MYOPATHIES

DR.PRAVEENNAGULA

ETIENNE JULES MAREY

HARVEY CUSHING

UNVERRICHT

ERNST LEBERECHT WAGNER

Basic muscle anatomy.physiology

INTRODUCTION MYOPATHY means primary skeletal muscle dysfunction. WASTING--- related to muscle MYALGIA– muscle pain FIBRILLATIONS - when muscle fibers lose contact with their

innervating axon producing a spontaneous action potential, "fibrillation potential" that results in the muscle fiber's contraction. not visible under the skin and are detectable through needle electromyography (EMG) and ultrasound.-pathological

FASCICULATIONS – visible spontaneuos contractions. SPASM/CRAMP – sudden PAINFUL involuntary contraction of

muscle TONE – continuous and partial contraction of the muscles AT

REST.resting muscle tension CLONUS –series of involuntary muscle contractions. MYOKYMIA – INVOLUNTARY ,groups of fasciculations –continuous

undualtions of muscle.

NERVOUS SYSTEM EXAMINATION In motor unit points in favour of myopathy : Muscle appearance – wasting ,atrophy (neurogenic) ABSENT fasciculations (+Denervation) Tenderness on palpation Tone –normal ,decreased in advanced cases. Distribution of weakness –proximal,distal (distal myopathies)

Pronator drift test Tendon reflexes – normal /hypoactive in adv.cases Babinski sign negative SENSORY system is normal. GAIT – lordosis on stance,increased on toe walking

Waddling gait – b/l pelvic girdle weakness Genu recurvatum –quadriceps weakness.

TYPE OF WEAKNESSINTERMITTENT MUSCLE WEAKNESS PERSISTENT WEAKNESS

SYMMETRIC

Atrophy asymmetric muscle weakness

Forearm flexors and quadriceps –PATHOGNOMONIC OF IBM

Dropped head syndrome

MG,ALS

Nemaline myopathy

Hyperparathyroidism

Focal myositis

IBM

APPROACH OF A PATIENT WITH INTERMITTENT WEAKNESS

Approach to a patient with PERSISTENT WEAKNESS

ONLY PTOSIS

MD

NEMALINE

NO PTOSIS

HYPERTHYROIDISM

Based on other complaintsFATIGUE Diff from asthenia

NMJ GLYCOLYSISLIPID ABNORMALITIES

MITOCHONDRIAL MYOPATHYCHRONIC MYOPATHY

MYALGIANO MUSCLE WEAKNESSFIBROMYALGIA

MYOFASCIAL SYN.

PMR,TEMPORAL ARTERITIS

MUSCLE WEAKNESSLOCAL -TRAUMA

CRAMPS +NMJDMD

MUSCLE CONTRACTUREGLYCOLYTICEMD

STIFFNESS

INFLAMMATION OF JOINTS

STIFFPERSON SYNDROME

NEUROMYOTONIA

•LIMB GIRDLE MUSCULAR DYSTOPHIES -

MUSCLE HYPERTROPHY

•DUCHENNE MUSCULAR DYSTROPHY

PSEUDOHYPERTROPHY

•HUMERAL MUSCLES - FSCHD•DYSFERLINOPATHIES -GASTROCNEMIUSATROPHY

EMG –assess the function of type I fibersnormal in steroid,disuse atrophy

EMG

IRRITABILITY ON NEEDLE PLACEMENT

INFLAMMATORY MYOPAT

HIESTOXIC

MYOPATHIES

DYSTROPHIESDIVE

BOMBER SIGNMYOTO

NIC MYOPAT

HY

NO IRRITABILITY

METABOLICMUSCULAR

DYSTROPHIESENDOCRINE

SHORT DURATIONSMALL AMPLITUDE

POLYPHASIC MOTOR UNIT ACTION POTENTIALS

NORMAL FIRING PATTER

N MYOPAT

HIES

FASTER FIRING NEUROGENIC

CAUSES

CLASSIFICATION 1.INFLAMMATORY /INFECTIOUS MYOPATHIES 2.CONGENITAL DISTAL MYOPATHIES 3.DISORDERS OF MUSCLE MEMBRANE EXCITABILITY 4.DRUG INDUCED/TOXIN INDUCED MYOPATHY 5.METABOLIC MYOPATHY 6.ENDOCRINE MYOPATHY 7.CRITICAL ILLNESS MYOPATHY 8.MITOCHONDRIAL MYOPATHIES 9.MUSCULAR DYSTROPHIES. 10.MISCELLANEOUS

INFLAMMATORY MYOPATIHES Largest group of acquired and potentially treatable causes of

skeletal muscle weakness . POLYMYOSITIS (PM) DERMATOMYOSITIS (DM) INCLUSION BODY MYOSITIS (IBM) 1 :1,00,000 PM – as alone is a rare disease affecting ADULTS. DM – affects both children,adults W>M IBM – M:F –3:1 ,caucasians,>50yrs.

PATHOGENESIS Autoimmune etiology - assosciation with other autoimmune

CTD ,various Auto Ab, MHC ,T CELL myotoxicity,complement, response to immunotherapy.

AUTOANTIBODIES AND IMMUNOGENETICS: 20% cases – ANA,anti cytoplasmic antigens Anticytoplasmic – anti RNP(anti synthetase), Anti jo 1 – 75% cases -80% assosciation with ILD. Anti Jo 1 –ILD ,RP,non erosive arthritis,MHCDR3,DRw52. DRB1 *0301,DQB1*0201 --- 75% PM,IBM DQA1*0501 –juvenile DM

IMMUNOPATHOGENIC MECHANISMS

DERMATOMYOSITIS: humoral immune mechanisms – microangiopathy. Endomysial inflammatory infiltrates -B cells auto AB -- complement pathway – C5b-9 membranolytic

complex- release of proinflammatory cytokines – VCAM1,ICAM 1 on endothelial cells – migration of lymphoid cells to perimysial and endomysial spaces---necrosis,microinfarcts.

Remaining capillaries dilated due to ischemia Perifascicular atrophy due to endofascicular hypoperfusion –

periphery of muscle fascicles.

IMMUNOPATHOGENIC MECHANISMS

POLYMYOSITIS,IBM : T cell mediated cytotoxicity CD8 T cells,macrophages –invade and destroy MHC 1 muscle

fibres(absent usually ) CD8/MHC 1 complex is characteristic of PM,IBM These cells have perforin,granzyme granules –myonecrosis. Antigen driven T cell response (auto AB in DM ) Antigens – endogenous (muscle),exogenous (viral) Co stimulatory molecules are upregulated .

ROLE OF NON IMMUNE FACTORS IBM : Degenerative process in addition to autoimmune process. B amyloid deposits within vacuolated muscle fibres,cyto ox –

ve mitochondria. Amyloid is APP,chymotrypsin,apoE,tau ?directly pathogenic /secondary MHC I upregulation – ER stress – accumulation of misfolded

glycoproteins ,NFkB –cytokine activation .

Association with viral infections Coxsackie,influenza,paramyxoviruses,mumps,CMV,EBV. Autoimmune myositis in coxsackie virus Molecular mimicry of Anti RNAsynthetase and genomic RNA . Best evidence of viral connection in PM,IBM –retroviruses. HIV,HTLV 1 – PM,IBM May be the initial manifestation or later of viral infection. Retroviral antigens –endomyosial macrophages ,but not in

muscle fibres. AZT induced myopathy –mitochondrial – ragged red fibres. AZT inhibits gamma DNA polymerase.

Clinical featuresIn general : PROGRESSIVE AND SYMMETRIC MUSCLE weakness (IBM –

asymmetric). Increasing difficulty with tasks – getting up from chair,climbing

steps,lifting objects,combing hair. Occular muscles are spared –even in advanced ,untreated

cases –if involved ? Diagnosis Head drop sign dysphagia Respiratory muscles involved in advanced cases. Muscle wasting in untreated cases . Sensation always normal . DTR preserved.

POLYMYOSITIS Subacute inflammatory myopathy affecting adults,rarely

children. Facial muscles are unaffected Diagnosis by exclusion. As an isolated entity it is rare. Commonly occurs in assosc.

With systemic autoimmune disease ,viral,bacterial. Drugs –AZT,D penicillamine

Who DONOT Have

1.Rash

2. EOM,facial muscles

3.Family H/O NMD

4.h/o myotoxic drugs,toxins

5.endocrinopathy

6.Neurogenic disease

7.Muscular dystrophy

8.Bicohemical disorder

9.IBM

DERMATOMYOSITIS Characteristic rash accompanying/preceding muscle weakness. –

increased photosensitivity Blue purple discoloration on the upper eyelids with edema.

(heliotrope rash) A flat red rash on the face and upper trunk. Erythema of the knuckles with a raised violaceous scaly eruption –

gottron’s sign . Erythematous rash on anterior chest – V sign. Back and shoulders – shawl sign . Dilated capillary loops at the base of the finger nails. Mechanic’s hands –irregular dirty horizontal lnies on the palmar

surface of fingers. Muscle tenderness,myalgia –connective tissue disease. Dermatomyositis sine myositis – muscle strength normal Perivascular perimysial inflammation

INCLUSION BODY MYOSITIS >50 yrs of age,most common inflammatory myopathy. Often misdiagnosed as PM Suspected when doesnot respond to therapy. Weakness and atrophy of distal muscles,foot extensors,deep

finger flexors –all cases –clue to early diagnosis. Fine motor movements –affected early Falling is common – quadriceps –buckling of knees. DTR –depressed in presence of atrophy . Dysphagia -60% cases Slow and steady progression Assisted devices required

Familial IBM 20 % CASES -systemic autoimmune or connective tissue

disease. Familial IBM Hereditary IBM - heterogenous group of recessive,dominant

inherited syndromes,non inflammatory May spare the quadriceps –iranian JEWS Chromosome 9p1 Mutations in the UDP – N acetylglucosamine 2- epimerase n –

acetylmannosamine kinase GNE gene.

Associated clinical findings EXTRAMUSCULAR MANIFESTATIONS: Systemic symptoms --- fever,malaise -- CTD. Joint contractures –DM in children Dysphagia ,GIabn – DM ,IBM Cardiac disturbances –arryhthmias,DCM,CCF Pulmonary dysfunction – ILD,drug induced – t RNA ab – 10% Subcutaneous calcifications –DM Arthralgias,deforming arthropathy – anti jo1 ab MALIGNANCIES – DM>PM,IBM Nasopharyngeal cancer in india Ovarian,breast,melanoma ,colon,NHL OVERLAP SYNDROMES – DM – SSc,PM – RA ,sjogren’s,SLE Anti PM/Scl - overlap syndrome of DM.

DIFFERENTIAL DIAGNOSIS SUBACUTE OR PROGRESSIVE MUSCLE WEAKNESS :

SPINAL MUSCULAR ATROPHY,ALS UMN signs ,denervation signs on EMG

MUSCULAR DYSTROPHIES – progress over years ,rarely present >30 yrs. RAPIDLY ADVANCING MUSCULAR dystrophy –fascio

scapulohumeral,dysferlin –inflammatory cell infiltration early. Trial of glucocorticoids,MHC/CD8

MYOPHOSPHORYLASE /ACID MALTASE deficiency ENDOCRINE TUMOR ASSOCIATED CACHEXIA LAMBERT EATON SYNDROME,MG

ACUTE MUSCLE WEAKNESS: GBS Transverse myelitis Poliomyelitis Myophosphorylase deficiency PARASITIC polymyositis. Tropical polymyositis –s.aureus Periodic paralysis Chronic ALCOHOLICS

MYOFASCITIS – skin induration -eosinophilic myofascitis NECROTIZING MYOSITIS – CK is high.ILD,CMP,anti SRP. DRUG INDUCED – d penicillamine Weakness due to muscle pain ,tenderness –PMR -type ii muscle

fibres,CFS –biopsy normal.

LAB INVESTIGATIONS 1.SERUM MUSCLE ENZYMES :most sensitive CK . Parallels disease activity (active -50 fold) Normal when CTD +PM,DM serumGOA,GPT,LDH,aldolase – elevated. 2.EMG – short duration,low amplitude polyphasic units on

voluntary activation,spontaneuous fibrillations,positive sharp waves.

Mixed potentials –IBM Identifies acute/chronic,excludes nuerogenic 3.MRI –muscle biopsy 4.muscle biopsy – definitive test Inflammation is the hallmark

Muscle biopsy POLYMYOSITIS – Primary – T cell infiltrates (endomyosial) surround healthy

muscle fibers- phagocytosis. CD8/MHC 1 –confirms the diagnosis. Alkaline phosphatase –react positively. DERMATOMYOSITIS – perivascular,interfascicular septae Intramuscular BV – endothelial hyperplasia Wedge shaped microinfarcts. Presence of perifascicular atrophy is diagnostic of DM in

absence of inflammation also. INCLUSION BODY MYOSITIS – rimmed vacuoles,fat

repalcement,ragged red fibres,amyloid deposits.

TREATMENT GOAL : improve muscle strength,ameliorate extramuscular

manifestations. Discontinue the drugs if after trial no improvement of muscle

strength. 1.GLUCOCORTICOIDS :oral prednisolone –high doses –

1mg/kg/day – 3-4 weeks,taper later 10 weeks – 1mg/kg every other day.

Lowest possible dose to be used. Efficacy by third month DM > PM in response. Steroid myopathy – increased weakness –2- 8 weeks.

Treatment cont… 2.IMMUNOSUPPRESSIVE THERAPY : 75% patients ultimately require. A.AZATHIOPRINE : 3mg/kg/day B.MTX : 7.5 mg weekly for the first 3 weeks -2.5mg/wk- 25 mg/wk --- MTX

pneumonitis. C.mycophenolate MOFETIL – 2.5 mg/d D.rituximab - IN DM E.CYCLOSPORINE – inconsistent benefit F.TACROLIMUS - PM difficult cases. 3.IMMUNOMODULATION: IVIg in refractory DM -short term benefit 2g/kg over 2-5 days /course PLASMAPHERESIS,LEUKOPHERESIS - NOT EFFECTIVE IN PM,DM

EMPIRICAL APPROACH IN TREATMENT

STEP 1 – HIGH DOSE PREDNISOLONE

HIGH DOSE PREDNISOLONE

AZATHIOPRINE,MYCOPHENOLATE,MTX

IVIG

Based on pt AGE,DISABILITY ,TOLERANCE – RITUXIMAB,CYCLOSPORINE,CYCLOPHOSPHAMIDE,TACROLIMUS(ILD)

NO RESPONSE TO TREATMENT IBM or metabolic myopathy,muscular dystrophy,endocrinopathy. Repeat muscle biopsy Calcinosis of DM –difficult to treat IBM –resistant to immunosupressive therapy Drugs not to be withdrawn IVIg and prednisolone – not effective

PROGNOSIS -5 yr surivival – 95%,10 yr -85% Death –pulmonary,cardiac Worse prognosis – older,severe mainfestations at prsentation DM responds favorably than PM,IBM IBM –least favorable prognosis.

ENDOCRINE MYOPATHIES Muscle fatigue is more common than true weakness. Serum CK LEVELS are normal. Muscle histology –atrophy rather than destruction. All respond to treatment THYROID DISORDERS: HYPOTHYROIDISM –proximal muscle weakness-1/3 Slow muscle contraction and relaxation -25% cases. Relaxation phase prolonged –ankle,biceps reflex Serum CK 10 times normal,EMG normal Muscle may be enlarged?,biopsy –no features

HYPERTHYROIDISM: Proximal muscle weakness,atrophy of

muscles. DTRs enhanced response. Bulbar,esophageal,respiratory muscles

affected. Fasciculations+DTRs –ALS misdiagnosis Acquired hypokalemic periodic

paralysis,MG,graves ophthalmopathy Serum CK levels are normal EMG is normal Muscle histology –atrophy of muscles

THYROID MYOPATHY

1.CHRONIC THYROTOXIC MYOPATHY

2.EXOPHTHALMOOPTHALMOPLEGIA

3.THYROTOXIC HYPOKALEMIC PERIODIC PARALYSIS

4.MYASTHENIA GRAVIS ASS WITH HYT.

5.HYPOTHYROID MYOPATHY

CHRONIC THYROTOXIC MYOPATHY – nodular goitre. Men>women. Basedow paraplegia. Atrophy – shoulder and hand muscles. Tremor twitches but not fasciculations GRAVES OPTHALMOPATHY- IR,MR,strabismus,diplopia Infiltrative opthalmopathy THYROTOXIC HPP- not familial,few hours,adult life. Hypothyroidism aggravates the weakness of MG Kocher -debre semelgaine syndrome,hoffmann syndrome

Adrenal disorders Most commonly diagnosed endocrine muscle disease. Proximal muscle weakness. Muscle wasting –striking feature+ cushingoid facies Type 2b fibres atrophy on histology Potassium depletion –CONN’S syndrome –NM complications. Serum CK LEVELS ELEVATED,vacuoles on biopsy. Vitamin D deficiency Parathyroid disorders –hypo,hyper PITUITARY DISORDERS DIABETES MELLITUS—THIGH muscles,pain tenderness in thigh Hard indurated muscle,vastus lateralis

CRITICAL ILLNESS MYOPATHY Acute quadriplegic myopathy/acute steroid myopathy In cases of severe asthma ,sepsis and shock. Neuromuscular blocking agents in 80% cases. High doses of corticosteroids 1mg/kg ,pancuronium -500-4,000 mg Difficulty in weaning from the ventilator Tendon relfexes are normal- diminished –polyneuropathy Serum CK levels elevated. EMG –MYOPATHY.type 2 fibers vacuolation. Striking loss of myosin filaments Severe cases– myoglobinuria,renal failure. Denervation of muscles –increase in glucocorticoid receptors Recovery over 6- 12 weeks

Neuromuscu

lar blocki

ng agents

Muscle

denervation -

Increase in the glucocorticoid recept

ors

Myosin

filaments loss

CARCINOMATOUS MYOPATHY Syndromes of NMJ – LAMBERT EATON SYNDROME,MG Syndromes of muscle – polymyositis /dermatomyositis,acute

necrotizing myopathy. ACUTE NECROTIZING MYOPATHY-rhabdomyolysis Painful myopathy Necrosis of muscle– raised CK,myoglobinuria Urine is cola coloured . Detected by radioimmunoassay Alkalinization of urine –nahco3 Mannitol,diuretics,IV fluids

DRUG INDUCED MYOPATHY MYOPATHY FROM LIPID LOWERING AGENTS GLUCOCORTICOID RELATED MYOPATHIES MYOPATHY OF NON DEPOLARIZING NEUROMUSCULAR BLOCKING

AGENTS DRUG INDUCED MITOCHONDRIAL MYOPATHY DRUGS OF ABUSE AND RELATED MYOPATHY DRUG INDUCED AUTOIMMUNE MYOPATHIES OTHER

• FIBRATES ,HMG COA ,NIACIN,EZETIMIBE• MYALGIA,MUSCLE TENDERNESS.• MUSCLE PAIN RELATED TO EXERCISE• RHABDOMYOLYSIS,MYOGLOBINURIA• ELEVTED CK LEVELS –TOXICITY – 3 TIMES – STOP THE DRUG• MYOPATHIC EMG-MUSCLE NECROSIS ON BIOPSY• IMPROVEMENT –SEVERAL WEEKS• NO RESPONSE – IMMUNE MEDIATED MYOPATHY-

GLUCOCORTICOIDS

LIPID LOWERING AGENTS

• HIGH DOSE IV GLUCOCORTICOIDS• >30 MG/DAY USE OF PREDNISOLONE• FLUORINATED GLUCOCORTICOIDS -TRIAMCINOLONE• SERUM CK NORMAL IN CHRONIC CASES• LOSS OF MYOSIN IN ACUTE ONSET.• RECOVERY SLOW IN ACUTE QUADRIPLEGIC MYOPATHY

GLUCOCORTICOID

MYOPATHIES

• DRUG RELATED INFLAMMATORY OR ANTIBODY MEDIATED

• WILSON’S,SCLERODERMA,RA,PBC• DRUG INDUCED POLYMYOSITIS -1%• MYASTHENIA GRAVIS – 7%• IMPROVE ON DRUG WITHDRAWAL.

D –PENICILLA

MINE

DISORDERS OF MUSCLE MEMBRANE EXCITABILITY• ADOLESCENCE,M>W,HIGH CARB DIET,REST AFTER

EXERCISE,CARDIAC ARRYHTHMIAS• TYPE 1 –AD,CALCIA3 GENE,10% TYPE 2 –SCN4• RX—ORAL KCL -0.2-0.4MMOL/KG EVERY 30 MIN(,MANNITOL)• LOW CARB,LOW SODIUM DIET,ACETAZOLAMIDE MAY ABOLISH

ATTACKS(NT IN TYPE2)

CALCIUM CHANNEL –HYPOKALEMIC

PERIODIC PARALYSIS

• MISNOMER – AD IN INHERITANCE• PROXIMAL MUSCLES ,BULBAR ARE SPARED.• MYOTONIA WITHOUT WEAKNESS –COLD STIFFNESS• LESS VACUOLES,MORE PERIPHERAL• ACETAZOLAMIDE,MEXILITINE

SODIUM CHANNEL –HYPERKALEMIC

PERIODIC PARALYSIS

• MYOTONIA WORSENS WITH MUSCULAR ACTIVITY• SENSORY,MOTOR NERVE CONDUCTION STUDIES ARE NORMAL• MYOTONIC DISCHARGES DISAPPEAR ON COOLING• AD,SODIUM CHANNEL• INCREASED CARBOHYDRATE IN THE DIET,MEXILITENE,THIAZIDE

DIURETICS

SODIUM CHANNEL PARAMYOTONIA

CONGENITA

POTASSIUM CHANNEL DISORDERS: 1.ANDERSEN TAWIL SYNDROME: Episodic weakness,dysmorphic features. cardiac arrythmias are life threatening. autosomal dominant –kir 2.1 gene Acetazolamide CHLORIDE CHANNEL DISORDERS: AD –THOMSEN’S DISEASE AR – BEKER’S DISEASE Myotonia worsened by cold,improved by activity Muscle strength normal in thomson’s Quinine,mexiletine,phenytoin.

DISTAL MYOPATHIES

Late onset,>40 yrsDominantly

inherited

WELANDER

Markesbery - Griggs

Udd ,tibial muscular

dystrophy

WELANDER MYOPATHY

WRIST ,FINGER EXTENSORS

•DOMINANT,TIBIAL WEAKNESS•CHILDHOOD IN ONSET•RIMMED VACUOLES ON BIOPSY

LAING DISTAL MYOPATHY

•AR inheritance.•NONAKA - -- ANTERIOR TIBIAL WEAKNESS•MIYOSHI – GASTROCNEMIUS.,ELEV.CK,ABSENT DYSFERLIN

NONAKA DISTAL,MIYOSH

I MYOPATHY

•AD/AR,CLINCALLY HETEROGENOUS•MYOTONIC DISCHARGES ON EMG•DENSE INCLUSION ON BIOPSY,DESMIN

MYOFIBRILLAR MYOPATHY

****LIMITED TO SKELETAL MUSCLES

CONGENITAL MYOPATHIES Specific histochemical and structural abn in muscle.

Central core disease

Breech presentation

Legs>armsCHD,scoliosis,pes cavus

Non progressiveSuspectible to malignant hyperthermia

CPK NORMAL CORES ON BIOPSY DEVOID OF

OXIDATIVE ENZYMES

CENTRONUCLEAR MYOPATHY

MARFANOID HABITUS

PROGRESSIVE EXTERNAL

OPHTHALOMPLEGIA,EOM WEAKNESS

CMT 2 SOMETIMESXp28

MYOTUBULARINArR –CHILDHOOD

NO SPECIFIC TREATMENT

METABOLIC MYOPATHIES

Ppted by brief

bursts of high

intensity exercise

Warm up exercise

helpful in mc ardles’s

diseaseHemolytic

anemia seen with

phosphofructokinase deficiency

Phosphoglycerate kniase –mental

retardation,Forear

m exercise

test

• Infantile form most common• Glycogen accumulation occurs in neurons• Childhood form –muscular dystrophy,only heart • Heart and liver not involved in

adult ,resp .failure

Acid maltase deficiency (pompe’s

disease)

• Slowly progressive• Diagnosed in infancy with hypotonia,hepatomegaly• hypoglycemia

Debranching enzyme deficiency

Type III glycogenosis

• Rare AND FATAL • HEPATOMEGALY• SKELETAL MUSCLE MANIFESTATIONS ARE MINOR

Branching enzyme deficiency

Type IV glycogenosis

MYOPHOSPHORYLASE DEFICIENCY(TYPE V)

PHOSPHOFRUCTOKINASE (TYPE VII)

BETA ENOLASE DEFICIENCY

Lipid abn myopathiesCarnitine

Palmiotyl transferase deficiency

Mc cause of recurrent myoglobinuria

Muscle pain only after the limit exceeded.

A normal rise in venous lactate on forearm exercise test

CPT II deficiency more common in men than womenHigh carb diet

MITOCHONDRIAL MYOPATHIES TERM RAGGED RED FIBRES –ABNORMAL MITOCHONDRIA ON MODIFIED

TRCIHROME STAIN . Mitochondria are enlarged,bizarrely shaped,crystalline inclusions Most common is CPEO >50% cases of mitochondrial myopathies.

KEARNS SAYRE SYNDROMEONSET<20 YRS,CPEO,PIGMENTARY RETINOPATHY PLUS

CHB,CSF PROTEIN >1 G/L,CERBELLAR ATAXIA

DEATH DUE TO HEART BLOCK -20%

ENDOCRINE ABN ARE COMMON –DIABETES MELLITUS -13%

MENTAL RETARDATION ,DEMENTIA

SERUM CK LEVLES NORMAL,SERUM LACTATE AND PYRUVATE LEVELS ELEVATED

MELAS

MOST COMMON MITOCHONDRIAL ENCEPHALOMYOPATHY

NO STRICT VASCULAR DISTRIBUTION-STROKE LIKE

STROKE <40 YRS AGE

DEMENTIA,BEDRIDDEN,FATAL STATE

SERUM LACTIC ACID ELEVATED

T RNA MUTATIONS -LETHAL

TYPE I FIBER ATPASE STAIN

W H I T E T R I C H R O M E S TA I N

Pure myopathy syndromes Affects only the muscle Recurrent myoglobinuria without fixed weakness and thus

resemble a glycogen storage or CPT deficiency. MITOCHONDRIAL DNA DEPLETION MYOPATHY : Clinically indistinguishgable from muscular dystrophy. Simulates DMD Seizures,CMP may be present. Serum CK 20-30 times normal,EMG –ragged red fibres. AR condition TK2 gene mutation 16 q22—supplies deoxyribonucleotides.

MISCELLANEOUS NEUROMYOTONIA –CONTINUOUS MUSCLE FIBER ACTIVITY. Hyperexcitability of terminal motor neuron plates. Rippling of muscle fibers – myokymia –main clinical sign. Walking is laborious –armadillo syndrome. Muscle activity during sleep. Curare abolishes. ISAAC syndrome

TRIALS 827 STUDIES ON MYOPATHIES MOLECULAR AND GENETIC STUDIES OF CONGENITAL MYOPATHIES. PHARMACOKINETIC STUDY ON N ACETYL NEURAMINIC ACID CHARACTERIZATION OF IBM WITH PAGET’S,FTD IS MYOPATHY PART OF STATIN THERAPY –IMPOSTER 16 STEM CELL TRANSPLANTATION IN IDIOPATHIC INFLAMMATORY

MYOPATHY DISORDERS ANAKINRA IN MYOSITIS THE EFFECT OF STATINS ON MUSCLE PERFORMANCE –STOMP STUDY METHIMAZOLE FOR DERMATOMYOSITIS ARIMOCOLOL IN SPORADIC INCLUSION BODY MYOSITIS LOG ON TO www.clinicaltrials.gov

TAKE HOME MESSAGE MYOPATHIES need to be categorised based on the pattern of

weakness intermittent,persistent. Usually present as proximal muscle weakness. The clinical examination reveals wasting>atrophy,DTR being normal. Laboratory wise raised CK levels normally. Confirmatory diagnosis by MUSCLE BIOPSY .EMG –normal. POLYMYOSITIS is usually seen in assosciation with other

disorders .diagnosis by exclusion. DERMATOMYOSITIS responds well to treatment. IBM can be misdiagnosed as PM Drug induced myopathy --- check the list for statins,steroids. Critical illness myopathy,neuropathy –increasing entity. Congenital distal myopathies,mitochondrial to be considered in D.D

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